Polyethylene glycol (PEG) coated liposomal nanoparticles of a defined size range of 100 to 200 nm are efficient drug delivery systems because they combine increased stability, high circulation times, increased tumor accumulation, and decreased systemic toxicity. Despite these particular advantages liposomal nanoparticles provide when compared to small molecule drugs, lack of selectivity for cancer cells still remains a major problem. An important feature of liposomal drug delivery nanoparticles is that they present particularly attractive scaffolds for the display of multiple functional groups on their surfaces. To overcome the selectivity problem, many researchers have taken the approach of active targeting by conjugating targeting ligands such as antibodies, antibody fragments, small molecules, and targeting peptides to improve the tumor targeting and cellular uptake of nanoparticle-based drug carriers. However, active targeting of nanoparticles has not consistently shown successful outcomes. At present, there is still an extensive debate on the relative contributions of active versus passive targeting in nanoparticle-based drug delivery systems. The apparent discrepancy observed in the field of targeted liposomal nanoparticles has in part been attributed to differences in type of tumor models. However, there is still a great amount of uncertainty regarding the source of the lack of consistent targeting outcomes.
Accordingly, there is a need for a nanoparticle drug delivery systems that can effectively target tumors and cancer cells for the delivery of active agents with reduced or eliminated systemic toxicity. There is also a need for novel nanoparticle drug delivery formulations and methods for delivering their drug cargo using pharmaceutically acceptable components that avoid immunogenic responses.